The United States Preventive Services Task Force recommends against the use of estrogen and progestin for the prevention of chronic medical conditions in postmenopausal women and the use of estrogen alone for the prevention of chronic conditions in postmenopausal women who have had a hysterectomy. Following a review of 51 articles published since 2002, the Task Force concluded that risks associated with these hormone replacement therapies (HRT) outweigh the chronic disease prevention benefits. The Task Force found that both estrogen alone and estrogen plus progestin reduce the risk for fractures, but increase risk for stroke, thromboembolic events, gallbladder disease, and urinary incontinence. Estrogen alone decreased risk for breast cancer. Estrogen plus progestin increased risk for probable dementia and breast cancer. The risk for breast cancer increased for women with prior oral contraceptive use, prior menopausal estrogen plus progestin therapy, or current smoking. The recommendations apply to average-risk women who have undergone menopause, and are not about the use of hormone therapy to treat symptoms of menopause, such as hot flashes or vaginal atrophy. These recommendations match the Task Force’s 2005 recommendations on HRT.

Note: For a PDF of the article, please contact Megan Hanks or Angela Collom. For an interview with an author, please contact Ana Fullmer at ana.fullmer@edelman.com or 202-350-6668.

Antibiotics not effective for cough due to ‘common cold’ in children

New research suggests that antibiotics are not effective in treating cough due to the common cold in children. The study, presented at CHEST 2012, the annual meeting of the American College of Chest Physicians, found that when children with acute cough were treated with either antitussive medication or antibiotics, antibiotics alone showed a lower percentage of cough resolution.

“In our experience, antibiotics are often prescribed by the general practitioner to treat cough in children, many times to pacify parents,” said lead study author Francesco de Blasio, MD, FCCP, Clinic Center Private Hospital, Naples, Italy. “However, antibiotics show very little effectiveness at treating cough due to your average head cold.”

To understand how antibiotics were being used in a clinical pediatric setting, Dr. de Blasio and colleagues from the University of Bologna and Dompé SPA in Italy observed the treatment and outcomes of 305 children who required pediatric consultation due to acute cough from the common cold. Of the children, 89 received antibiotics only, while 38 received a combination of antibiotics and antitussives; central (codeine and cloperastine) in 16 cases, and peripheral (levodropropizine) in 22 children. Forty-four and 79 children received only central or peripheral antitussives, respectively, without antibiotics; 55 children did not receive medication.

Observational results showed no difference in percentage of cough resolution between children treated with antitussive alone vs children receiving a combination of antibiotics and antitussives. On the contrary, children treated with antibiotics only had a lower percentage of cough resolution than children treated with antitussive only. Furthermore, the use of the peripheral antitussive levodropropizine demonstrated a significant beneficial effect in terms of cough resolution compared with centrally acting antitussive drugs (47% vs28%).

“Few drugs are effective as cough suppressants, and antibiotics are no more effective in relieving cough than the use of no medication,” he added. “However, peripheral antitussives, such as levodropropizine, appear to be the best option at relieving cough.”

Dr. de Blasio’s results support the American College of Chest Physicians evidence-based guidelines for the diagnosis and management of cough, published in the journal CHEST in 2006, which recommend the use of peripheral antitussives for certain types of cough. Although antibiotics may not be an effective therapy for cough, they can be useful in treating underlying infections that may produce cough, adds Dr. de Blasio. But he warns that antibiotics should not be overused. “Using antibiotics as a treatment for cough without suspected infection is unnecessary and can be harmful,” explained Dr. de Blasio. “Repeated use of antibiotics, especially when they are ineffective, can lead to adverse allergic reactions or a resistance to the medications.”

“As parents, it is difficult to watch our children suffering from a terrible cough, but turning to antibiotics is not always the answer,” said ACCP President-Elect Darcy D. Marciniuk, MD, FCCP. “Depending on the underlying cause of the cough, a health-care professional can recommend the best treatment options for a child, which, in some cases, may be no treatment.”

Exercise may trump mental activity in protecting against brain shrinkage

MINNEAPOLIS – Exercising regularly in old age may better protect against brain shrinkage than engaging in mental or social activities, according to a new study published in the October 23, 2012, print issue of Neurology®, the medical journal of the American Academy of Neurology. Research suggests that brain shrinkage may lead to problems with memory and thinking.

“People in their seventies who participated in more physical exercise, including walking several times a week, had less brain shrinkage and other signs of aging in the brain than those who were less physically active,” said study author Alan J. Gow, PhD, with the University of Edinburgh in Scotland. “On the other hand, our study showed no real benefit to participating in mentally and socially stimulating activities on brain size, as seen on MRI scans, over the three-year time frame.”

Researchers looked at medical records of 638 people from Scotland born in 1936. The participants were given MRI scans at 73 years old.

The group gave details about their exercise habits, ranging from moving only in connection with necessary household chores to keeping fit with heavy exercise or participating in competitive sports several times per week. They also reported their participation in social and mentally stimulating activities.

The study found that after three years, people who participated in more physical activity experienced less brain shrinkage than those who exercised minimally.

“Our results show that regularly exercising in old age is potentially important to protecting the brain as we age,” said Gow.

Selenium deficiency may cause cardiomyopathy post-gastric bypass

Las Vegas, NV (October 22, 2012) –-Non-compliance with vitamin and mineral supplementation protocols after bariatric surgery could lead to nutritional deficiencies and related health complications, such as heart damage, according to two separate case reports unveiled today at the American College of Gastroenterology’s (ACG) 77th Annual Scientific meeting in Las Vegas.

Multivitamin supplementation is considered the standard of care for any patient undergoing gastric bypass, according to researchers from the University of Missouri who report a case of a non-compliant patient who failed to maintain regular follow-up after undergoing bariatric surgery leading to severe vitamin and mineral deficiencies managed by a multidisciplinary approach.

In this case, a 38-year old female patient underwent Roux-en-Y (RYGB) gastric bypass surgery but had limited follow-up during the five years since her surgery when she presented with several weeks of fatigue. She lost nearly 104 pounds since her surgery and was poorly compliant with her vitamin and mineral supplements, according to co-investigator Hazem Hammad, M.D.

“When she came in for medical care she was pale and had a slight soft ejection systolic murmur,” said Dr. Hammad, who noted that she had hemoglobin of 4.7 g/dL and marked mineral and vitamin deficiencies, including low levels of Vitamin B12, Vitamin D, Zinc, and Iron. After receiving counseling about the crucial benefits from long term follow-up and compliance with vitamin supplements, the patient was discharged to complete an IV iron supplementation treatment course and to follow up with a bariatric surgery multidisciplinary center, according to the case report. Two weeks following discharge she received additional counseling from her primary care physician and was given a handout that outlined vitamin supplementation following bariatric surgery along with written information that included how to obtain bariatric vitamins via website, phone and from pharmacies.

Three months following discharge laboratory tests revealed an increase in hemoglobin to 10.8 g/dL and an improvement in her vitamins and mineral deficiency status.

“The pre- and post-operative management of bariatric surgery patients is clearly multidisciplinary. United States guidelines define the primary team as comprising the bariatric surgeon, the obesity specialist and the dietitian,” said Dr. Hammad. “Primary care physicians, however, have a significant role in managing and following these patients by providing crucial patient education and support as illustrated in our case.”

Crusty foods may worsen heart problems associated with diabetes

URBANA – A University of Illinois study suggests avoiding cooking methods that produce the kind of crusty bits you’d find on a grilled hamburger, especially if you have diabetes and know you’re at increased risk for cardiovascular disease because of your diagnosis.

“We see evidence that cooking methods that create a crust—think the edge of a brownie or the crispy borders of meats prepared at very high temperatures—produce advanced glycation end products (AGEs). And AGEs are associated with plaque formation, the kind we see in cardiovascular disease,” said Karen Chapman-Novakofski, a U of I professor of nutrition.

For years nutrition experts have advised people with diabetes to bake, broil, or grill their food instead of frying it, she said.

“That’s still true, but if you have diabetes, you should know that AGEs—byproducts of food preparation methods that feature very high, intense, dry heat—tend to end up on other tissues in the body, causing long-term damage,” she added.

In the U of I study, the scientists compared the 10-day food intake of 65 study participants in two ethnic groups: Mexicans (who have higher rates of diabetes and a greater risk of complications from the disease) and non-Hispanic whites.

“We found that people with higher rates of cardiovascular complications ate more of these glycated products. For each unit increase in AGEs intake, a study participant was 3.7 times more likely to have moderate to high risk for cardiovascular disease,” said Claudia Luevano-Contreras, first author of the study.

The study showed that non-Hispanic whites had a higher intake of AGEs, and they consumed more saturated fats. However, the association between AGEs and cardiovascular disease was stronger than for saturated fats and heart disease, she said.

Eating less saturated fat and more fruits, vegetables, and fiber are important for people with diabetes, but this study shows that food preparation may be important too, she added.

“AGEs are higher in any kind of meat, but especially in ground meat,” she said. “If you put hamburgers or brats on the grill, you’ll likely have a higher AGEs content than if you chose a whole cut of meat, say round steak or chicken,” said Chapman-Novakofski.

Boiling or stewing meat would reduce your AGEs intake further. And scrambling an egg with cooking spray instead of frying it leads to a significant reduction in AGEs, she added.

The scientists said more research is needed before definite recommendations can be made. They are planning another study in which they’ll examine past AGEs intake of diabetes patients.

“These findings are preliminary, but they give us ample reason to further explore the association between AGEs and cardiovascular risk among people with diabetes,” Chapman-Novakofski noted

New vitamin-based treatment that could reduce muscle degeneration in muscular dystrophy

Boosting the activity of a vitamin-sensitive cell adhesion pathway has the potential to counteract the muscle degeneration and reduced mobility caused by muscular dystrophies, according to a research team led by scientists at the University of Maine.

The discovery, published 23 October in the open access journal PLOS Biology, is particularly important for congenital muscular dystrophies, which are progressive, debilitating and often lethal diseases that currently remain without cure. The researchers found that they could improve muscle structure and function in a zebrafish version of muscular dystrophy by supplying a common cellular chemical (or its precursor, vitamin B3) to activate a cell adhesion pathway.

Muscle cells are in themselves relatively delicate, but derive important additional mechanical strength from adhesion protein complexes; these anchor the muscle cells to an external framework known as the basement membrane, thereby helping to buffer the cells against the extreme forces that they experience during muscle contractions. Mutations in the genes that encode these adhesion proteins can weaken these attachments, making muscle cells more susceptible to damage and death.

The resulting muscle degeneration can eventually lead to progressive muscle-wasting diseases, such as muscular dystrophies. A major component of the basement membrane, a protein called laminin, binds to multiple different receptors on the muscle cell surface and forms a dense, organized network.

The study was led by UMaine Associate Professor of Biological Sciences, Clarissa Henry, whose laboratory focuses on understanding how cell adhesion complexes contribute to muscle development. The researchers discovered that a pathway involving a common cellular chemical called nicotinamide adenine dinucleotide (NAD+) plays a role in the formation of organized basement membranes in muscle tissue, during development of the fish embryo. As disordered basement membranes are seen in many different types of muscular dystrophies, the researchers wondered whether activating this pathway might reduce the severity of some muscular dystrophies.

In the current study, the researchers show that NAD+ improves the organization of laminin in a zebrafish version of muscular dystrophy. Zebrafish lacking either of the two main receptors for laminin have a disorganized basement membrane, causing muscle degeneration and difficulties with movement. However adding extra NAD+, or even a vitamin packet containing vitamin B3 (niacin, a precursor to NAD+), significantly reduced these symptoms.

The research team found that the main protective effects of NAD+ come from enhancing the organization of the laminin structure in the basement membrane, which helps to increase the resilience of diseased muscle fibers.

Because the same cell adhesion complexes are found in humans, the research team is optimistic that these findings may one day positively impact patients with muscular dystrophies. “Although there is a long way to go, I’m hopeful that our data could eventually lead to new adjuvant therapies,” says University of Maine Ph.D. student Michelle Goody, who led the research team with Prof. Henry.

Prof. Henry summarizes; “One of my favorite aspects of this study is that it is a poster child for how asking basic biological questions can lead to exciting discoveries that may have future therapeutic potential.”

The flame-retardant mixture known as “Firemaster 550” is an endocrine disruptor that causes extreme weight gain, early onset of puberty and cardiovascular health effects in lab animals, according to a new study spearheaded by researchers from North Carolina State University and Duke University.

Firemaster 550 is made up of four principal component chemicals and is used in polyurethane foam in a wide variety of products, ranging from mattresses to infant nursing pillows. The flame-retardant mixture was developed by Chemtura Corp., and was first identified by the research community in 2008. It was developed to replace a class of fire retardants being phased out of use because of concerns regarding their safety. This new study represents the first public data on whether Firemaster 550 has potential health effects.

In this pilot study, pregnant lab rats were assigned to three groups: a control group, which was not exposed to Firemaster 550; a “low-dose” group, which ingested 100 micrograms of Firemaster 550 once per day throughout pregnancy and nursing; and a “high-dose” group, which ingested 1,000 micrograms on the same schedule. These environmentally relevant doses are lower than the doses used in industry-funded studies. Researchers then evaluated the physiological outcomes of the exposure in both the mothers (called dams) and the offspring (called pups).

Importantly, the researchers detected TBB, one of Firemaster 550’s component chemicals, in the fat of all the exposed dams and offspring, but none of the unexposed animals. This means the flame retardant is capable of crossing the placenta during pregnancy, reaching infants via breast milk, or both.

Because flame retardants that have been phased out are known to disrupt thyroid function, and Firemaster 550 includes chemicals with structural similarities, the researchers looked at circulating thyroid hormone levels in dams at the end of the nursing period. The high-dose dams had much higher thyroid hormone levels than the control group, while low-dose dams had marginally higher thyroid hormone levels. This is significant because thyroid hormones influence brain development during pregnancy, as well as a host of other biological functions, such as metabolism.

Researchers also found extremely rapid weight gain in the offspring. By the time they were weaned from nursing, high-dose male pups were 60 percent heavier than the control group – and high-dose female pups were 31 percent heavier than the control group.

The increased weight in female pups contributed to the early onset of puberty. The control group hit puberty at 33 days old, while the high-dose group hit puberty at 29 days.

High-dose female pups also had difficulty regulating their glucose levels as adults. High-dose males had thickened walls in the left ventricle of the heart, suggestive of cardiovascular disease.

“This study indicates that Firemaster 550 is an endocrine disruptor, and that raises a lot of important questions,” says Dr. Heather Patisaul, an assistant professor of biology at NC State and lead author of a paper describing the work. “This was a small-scale study. We need to continue this work with a larger sample size and look at a broader range of potential effects related to obesity, thyroid hormone function and metabolic syndrome. We also want to determine which of the component chemicals in Firemaster 550 are responsible for the various effects.”

The paper, “Accumulation and Endocrine Disrupting Effects of the Flame Retardant Mixture Firemaster 550 in Rats: An Exploratory Assessment,” is published online in the Journal of Biochemical and Molecular Toxicology. Co-authors include NC State undergraduate Natalie Mabrey; NC State research technician Katherine McCaffrey; Heather Stapleton and Simon Roberts of Duke University; Robin Gear and Scott Belcher of the University of Cincinnati; and Joe Braun of Brown University. The research was funded by the National Institute of Environmental Health Sciences

Scripps Research Institute Study Suggests Caution and Further Studies on Drugs Used to Treat Macular Degeneration

LA JOLLA, CA – October 24, 2012 – Millions of people with “wet” macular degeneration are prescribed a class of medication known as anti-VEGF drugs. But now scientists at The Scripps Research Institute (TSRI) have found that a drastic reduction of VEGF activity may do more harm than good.

In the new study, the researchers deleted the gene for the blood-vessel growth factor VEGF, which has been implicated in stimulating abnormal blood vessel growth in a range of cancers and eye diseases, from cells in the retinas of adult mice. The results showed that without VEGF a large subset of light-sensing cells lost their main blood supply and shut down, causing severe vision loss.

“It’s becoming clear that VEGF has a critical function in maintaining the health of the retina, and we need to preserve that critical function when we treat VEGF-related conditions,” said TSRI Professor Martin Friedlander, MD, PhD, senior author of the new study, which appears in the November 2012 issue of the Journal of Clinical Investigation.

Major Target for Drug Developers

VEGF (vascular endothelial growth factor) has long been a major target for drug developers. Tumors often overproduce VEGF to stimulate local blood vessel growth and thus keep their fast-dividing cells well supplied with oxygen and nutrients. Low-oxygen conditions in the eyes of elderly or diabetic individuals also can trigger the overproduction of VEGF, resulting in a vision-destroying bloom of abnormal, leaky retinal blood vessels.

Several anti-VEGF drugs (such as Lucentis® (ranibizumab), Macugen (pegaptanib), Eylea® (aflibercept) and Avastin® (bevacizumab)) are already in use, and dozens more are in clinical trials against cancers and common eye disorders such as wet macular degeneration.

However, to date there have not been extensive studies on the effects of such drugs on the normal role of VEGF, in part because it is hard to generate adult animals that lack the VEGF gene. When the gene is removed from the embryos of mice, in a standard“knockout” experiment, the mice fail to develop normally and die before birth.

New Insights

In the new study, Friedlander laboratory postdoctoral fellows Toshihide Kurihara, MD, PhD, and Peter D. Westenskow, PhD, found a way to delete the major VEGF gene from mice after the animals had grown to adulthood. To determine VEGF’s role in the retina, they confined the gene deletion to the animals’ retinal pigment epithelial cells, which nourish and repair the retina and are a major retinal source of VEGF. The result suggests that VEGF does have a crucial function in the adult retina.

“Only three days after we knocked down the gene, we observed the complete deterioration of the choriocapillaris, a layer of capillaries that is a major supplier of nutrients to the outer retina, the location of the rod and cone photoreceptors,”said Kurihara.

Nearby light-sensing cone cells, which are specialized for detecting color and fine detail in visual images, also rapidly lost their function, causing pronounced vision loss in the mice. Seven months after the knockdown of the VEGF gene, the retinal damage and vision loss were still evident. “The deterioration seems irreversible if VEGF is not present,” said Westenskow.

Rod cells, which support low-light and peripheral vision, were not affected by the VEGF-gene deletion. The researchers note that cone cells may be more vulnerable because they are unusually active metabolically and may be unable to withstand a significant decrease in blood supply. Cone cells also bear receptors for VEGF molecules and thus may require direct VEGF stimulation to remain healthy. In any case, even if only cone cells died and rod cells were spared, a patient would experience severe vision loss. “You’d be defeating your purpose if you dried up the abnormal blood vessel growth but at the same time killed off the cone cells,” said Friedlander.

Paths for Future Research

Whether such side effects are happening with existing anti-VEGF treatments is unclear. While these assessments are possible, but they have been considered prohibitively expensive and invasive.

Friedlander, however, now believes such studies are necessary and plans to conduct such assessments in eye-disorder patients—who typically receive direct injections of anti-VEGF drugs to their eyes—to determine whether the drugs are causing these adverse side effects. He notes that the evaluations may be particularly necessary for a new class of anti-VEGF drugs recently approved for use in the treatment of age-related macular degeneration—drugs that are much more potent and persistent than previous anti-VEGF agents.

Fortunately, anti-VEGF drugs are not the only possible strategy for treating pathological blood vessel growth, as the new study makes clear. VEGF-related tumors and eye conditions also involve the overproduction of low-oxygen signaling proteins known as HIFs. The team found that deleting the genes for these HIFs in retinal cells largely prevents blood vessel overgrowth in a standard mouse model—without affecting the normal-level production of retinal VEGF or causing eye damage.

“In light of the present findings, other strategies for treating these eye conditions could be a possibility,” Friedlander said. “Conceivably, an anti-HIF treatment could also be combined with an anti-VEGF treatment, allowing the dose of the latter to be lowered significantly.”

The Friedlander lab, in collaboration with the laboratories of David Cheresh, PhD, and Michael Sailor, PhD, of the University of California, San Diego, has also been exploring the potential utility of inhibiting microRNAs that regulate angiogenic genes further upstream to VEGF. This work is being supported by a $10 million grant from the National Eye Institute and could lead to the development of antagonists that avoid the off-target effects of VEGF inhibitors.

In addition to Friedlander, Kurihara and Westenskow, other contributors to the study, “Targeted deletion of Vegfa in adult mice induces vision loss,” were Stephen Bravo and Edith Aguilar, both of TSRI. For more information on the paper, see http://www.jci.org/articles/view/65157.

The study was supported in part by grants from the National Eye Institute of the National Institutes of Health (EY-11254, EY-021416), the Lowy Medical Research Institute, the Manpei Suzuki Diabetes Foundation and The Japan Society for the Promotion of Science.

In a new study out today, researchers used mice to identify a combination six naturally occurring bacteria that eradicate a highly contagious form of Clostridium difficile, an infectious bacterium associated with many hospital deaths. Three of the six bacteria have not been described before. This work may have significant implications for future control and treatment approaches.

The researchers found that this strain of C. difficile, known as O27, establishes a persistent, prolonged contagious period, known as supershedding that is very difficult to treat with antibiotics. These contagious ‘supershedders’ release highly resistant spores for a prolonged period that are very difficult to eradicate from the environment. Similar scenarios are likely in hospitals.

C. difficile can cause bloating, diarrhoea, abdominal pain and is a contributing factor to over 2,000 deaths in the UK in 2011. It lives naturally in the body of some people where other bacteria in the gut suppress its numbers and prevent it from spreading. If a person has been treated with a broad-spectrum antibiotic such as clindamycin, our bodies’ natural bacteria can be destroyed and the gut can become overrun by C. difficile. The aggressive strain of C. diff analysed in this study has been responsible for epidemics in Europe, North America and Australia.

“We treated mice infected with this persistent form of C. diff with a range of antibiotics but they consistently relapsed to a high level of shedding or contagiousness,” says Dr Trevor Lawley, first author from the Wellcome Trust Sanger Institute. “We then attempted treating the mice using faecal transplantation, homogenized faeces from a healthy mouse. This quickly and effectively supressed the disease and supershedding state with no reoccurrence in the vast majority of cases.”

“This epidemic caused by C. diff is refractory to antibiotic treatment but can be supressed by faecal transplantation, resolving symptoms of disease and contagiousness.”

The team wanted to take this research one step further and isolate the precise bacteria that supressed C. diff. and restored microbial balance of the gut. They cultured a large number of bacteria naturally found in the gut of mice, all from one of four main groups of bacteria found in mammals. They tested many combinations of these bacteria, until they isolated a cocktail of six that worked best to suppress the infection.

“The mixture of six bacterial species effectively and reproducibly suppressed the C. difficile supershedder state in mice, restoring the healthy bacterial diversity of the gut,” says Professor Harry Flint, senior author from the University of Aberdeen.

The team then sequenced the genomes of the six bacteria and compared their genetic family tree to more precisely define them. Based on this analysis, the team found that the mixture of six bacteria contained three that have been previously described and three novel species. This mix is genetically diverse and comes from all four main groups of bacteria found in mammals.

These results illustrate the effectiveness of displacing C. diff and the supershedder microbiota with a defined mix of bacteria, naturally found in the gut.

“Our results open the way to reduce the over-use of antibiotic treatment and harness the potential of naturally occurring microbial communities to treat C. difficile infection and transmission, and potentially other diseases associated with microbial imbalances,” explains Professor Gordon Dougan, senior author from the Wellcome Trust Sanger Institute. “Faecal transplantation is viewed as an alternative treatment but it is not widely used because of the risk of introducing harmful pathogens as well as general patient aversion. This model encapsulates some of the features of faecal therapy

Feinstein Institute researchers discover that bean used in Chinese food could protect against sepsis

MANHASSET, NY – Researchers at The Feinstein Institute for Medical Research have discovered that a bean commonly used in Chinese cuisine protects against the life-threatening condition sepsis. These findings are published in the current issue of Evidence-based Complementary and Alternative Medicine (eCAM).

It has been found that a deoxyribonucleic acid (DNA) protein, HMGB1, mediates inflammation. Inflammation is necessary for maintaining good health – without inflammation, wounds and infections would never heal. However, persistent and constant inflammation can damage tissue and organs, and lead to diseases such as sepsis. Sepsis affects approximately 750,000 Americans each year, 28 to 50 percent of whom die from the condition, and costs the nation’s healthcare system nearly $17 billion annually. It is a potentially life-threatening complication of an infection or injury, and occurs when chemicals released into the bloodstream to fight the infection trigger inflammation throughout the body. The result is that organs become damaged, including liver, heart, lungs, kidney, and brain. If excessive damage occurs, it may be irreversible. Therefore, it is important to identify ways in which persistent and constant inflammation can be halted.

Neutralizing the protein HMGB1 protects against persistent and constant inflammation that results in damage to tissue and organs. Haichao Wang, PhD, and his colleagues, including Shu Zhu, MD and PhD, and Andrew E. Sama, MD, at the Feinstein Institute found that extract from mung bean (Vigna radiata), a bean native to India and commonly used in Chinese food and traditional medicine, reduced the release of HMGB1, thereby increasing survival rates in mice from 29.4 percent to 70 percent (P < 0.05).

“Many traditional medicinal herbs have been successfully developed into effective therapies for various inflammatory ailments, and now we have validated the therapeutic potential of another medicinal product, mung bean extract,” said Dr. Wang. “Demonstrating that mung bean extract has a positive effect on septic mice shows promise that this bean can also have a positive effect on septic humans – of course, additional studies are required to prove the safe and effective use in humans.”

Drop in testosterone tied to prostate cancer recurrence

Drop in testosterone tied to prostate cancer recurrence

Fox Chase researchers find that men whose testosterone falls after radiation are more likely to experience a rise in PSA

BOSTON, MA (October 28, 2012)—Men whose testosterone drops following radiation therapy for prostate cancer are more likely to experience a change in PSA levels that signals their cancer has returned, according to new research from Fox Chase Cancer Center. The findings will be presented on October 29 at the American Society for Radiation Oncology’s 54th Annual Meeting.

Specifically, men whose testosterone fell following various forms of radiation therapy were more likely to experience an increase in prostate-specific antigen (PSA)—often the first indication the cancer has recurred.

“The men who had a decrease in testosterone also appear to be the men more likely to see an increase in PSA after treatment,” says study author Jeffrey Martin, MD, resident physician in the Department of Radiation Oncology at Fox Chase.

In theory, doctors may one day be able to use testosterone levels to guide treatment decisions, says Martin. “For men with a decrease in testosterone, doctors might intervene earlier with other medications, or follow their PSA more closely than they would otherwise, to spot recurrences at an earlier time.”

Martin and his colleagues decided to conduct the study because there is limited information regarding testosterone levels after radiation treatment and what it means for prognosis. To investigate whether a decrease in testosterone has any clinical effects, Martin and his colleagues reviewed medical records from nearly 260 men who received radiation therapy for prostate cancer between 2002 and 2008. The men were treated with either brachytherapy, in which doctors insert radioactive seeds in the prostate, or intensity modulated radiation therapy (IMRT), in which an external beam of radiation is directed at the prostate.

The researchers found that testosterone levels tended to decrease following both forms of radiation therapy. And men who experienced a post-radiation drop in testosterone— particularly a significant drop—were more likely to see their PSA levels rise during the follow-up period.

Still, an increase in PSA—known as biochemical failure—was relatively rare, the authors found. “Only 4% of patients with low-risk prostate cancer had biochemical failure at five years,” says Martin.

Even though researchers have seen testosterone decrease following another form of radiation, these latest findings are still somewhat surprising, says Martin, because testosterone is believed to drive prostate cancer. In fact, some patients with advanced forms are prescribed hormone therapy that attempts to knock down testosterone.

“Seeing that a drop in testosterone is tied to recurrence is kind of a surprising result,” says Martin. “We don’t necessarily know what this means yet. I think the relationship between testosterone levels following radiation therapy and prognosis needs more study, and until then it’s premature to say this is something patients should ask their doctors about.”

This was a small study that needs to be validated in a larger group of men before doctors begin basing their predictions of recurrence on patients’ testosterone levels, he cautions. “I think the link between testosterone and PSA needs more study, in a larger set of patients.”

Exercise is smart for your heart – and makes you smarter

Study shows that high-intensity training boosts cognitive function

A regular exercise routine can make you fitter than ever – mentally fit.

In a new study, previously sedentary adults were put through four months of high-intensity interval training. At the end, their cognitive functions – the ability to think, recall and make quick decisions – had improved significantly, says Dr. Martin Juneau, director of prevention at the Montreal Heart Institute.

“If you talk to people who exercise, they say they feel sharper. Now we’ve found a way to measure that,” says Dr. Juneau.

Blood flow to the brain increases during exercise. The more fit you are, the more that increases. The pilot study – presented today at the Canadian Cardiovascular Congress – looked at adults, average age 49, who were overweight and inactive. Dr. Juneau and his colleagues measured their cognitive function with neuropsychological testing, as well as their body composition, blood flow to the brain, cardiac output and their maximum ability to tolerate exercise.

The subjects then began a twice-a-week routine with an exercise bike and circuit weight training. After four months – not surprising – their weight, body mass index, fat mass and waist circumference were all significantly lower. Meanwhile, their capacity to exercise (measured by VO2 max) was up 15 per cent.

Most exciting, says Dr. Juneau, cognitive function had also increased, based on follow-up testing. These improvements were proportional to the changes in exercise capacity and body weight. Essentially, the more people could exercise, and the more weight they lost, the sharper they became.

A decline in cognitive function is a normal part of aging, notes Dr. Juneau. That drop can be worse for people who have coronary disease.

“It’s reassuring to know that you can at least partially prevent that decline by exercising and losing weight,” says Dr. Juneau.

As he notes, people can manage their cholesterol or blood pressure with a pill, but try to find a pill that will increase your cognitive function. Exercise, he says, can do it all.

“At least 150 minutes of moderate-to-vigorous physical activity per week can make a huge difference to manage risk factors for heart disease and stroke,” says Dr. Beth Abramson, Heart and Stroke Foundation spokesperson. “There are many benefits of exercise – we know it can make us feel better. This suggests it can make us ‘think better’ as well.”

“Activity can help you even if it’s spread out in chunks of 10 minutes or more at a time,” she says. “In fact, to get the most benefit, add more activity to your life over several days of the week.”

New study reveals that every single junk food meal damages your arteries

A single junk food meal – composed mainly of saturated fat – is detrimental to the health of the arteries, while no damage occurs after consuming a Mediterranean meal rich in good fats such as mono-and polyunsaturated fatty acids, according to researchers at the University of Montreal-affiliated ÉPIC Center of the Montreal Heart Institute. The Mediterranean meal may even have a positive effect on the arteries. The findings are being presented at the Canadian Cardiovascular Congress, which runs in Toronto until Wednesday, by the head of the study, Dr. Anil Nigam, Director of Research at the Cardiovascular Prevention and Rehabilitation Centre (ÉPIC) and associate professor at the university’s Faculty of Medicine.

Bad fat vs. good fat

Dr. Nigam undertook the study to compare the effects of junk food and typical Mediterranean meal on the vascular endothelium: the inner lining of the blood vessels. By measuring endothelial function, it is possible to determine how easily the arteries will dilate after a temporary, five-minute occlusion, following the consumption of the two types of meals. This is a very interesting analysis for researchers to perform as endothelial function is closely linked to the long-term risk of developing coronary artery disease.

The study also revealed that participants with higher blood triglyceride levels seemed to benefit more from the healthy meals. Their arteries responded better to the Mediterranean meal compared to people with low triglyceride levels. “We believe that a Mediterranean-type diet may be particularly beneficial for individuals with high triglyceride levels, such as patients with metabolic syndrome, precisely because it could help keep arteries healthy,” Dr. Nigam said.

Mediterranean meal vs. junk food meal

The results were established in 28 non-smoking men, who ate the Mediterranean-type meal first and then the junk food-type meal one week later. Before beginning, the men underwent an ultrasound of the antecubital artery at the elbow crease after fasting for 12-hours to assess their baseline endothelial function. The researchers then tested the effects of each meal. The first was composed of salmon, almonds, and vegetables cooked in olive oil, of which 51% of total calories came from fat (mostly monounsaturated fatty acids and polyunsaturated fats.) The second meal consisted of a sandwich made of a sausage, an egg, and a slice of cheese, and three hash browns, for a total of 58% of total calories from fat: extremely rich in saturated fatty acids and containing no omega-3s. At two hours and four hours after each meal, participants underwent further ultrasounds to assess how the food had impacted their endothelial function.

Dr. Nigam and his team found that after eating the junk food meal, the arteries of the study participants dilated 24% less than they did when in the fasting state. In contrast, the arteries were found to dilate normally and maintain good blood flow after the Mediterranean-type meal.

“These results will positively alter how we eat on a daily basis. Poor endothelial function is one of the most significant precursors of atherosclerosis. It is now something to think about at every meal,” Dr. Nigam said.

Common food preservative may slow, even stop tumor growth

ANN ARBOR—Nisin, a common food preservative, may slow or stop squamous cell head and neck cancers, a University of Michigan study found.

What makes this particularly good news is that the Food and Drug Administration and the World Health Organization approved nisin as safe for human consumption decades ago, says Yvonne Kapila, the study’s principal investigator and professor at the University of Michigan School of Dentistry.

This means that obtaining FDA approval to test nisin’s suggested cancer-fighting properties on patients in a clinical setting won’t take as long as a new therapy that hasn’t been tried yet on people, she says.

Antibacterial agents like nisin alter cell properties in bacteria to render it harmless. However, it’s only recently that scientists began looking to antibacterial agents like nisin to see if they altered properties in other types of cells, such as cancer cells or cells in tumors.

Oral cancer is a leading cause of death worldwide, and oral squamous cell carcinoma accounts for more than 90 percent of oral cancers. However, survival rates for oral cancer haven’t improved in decades, according to the study.

“The poor five-year survival rates for oral cancer underscore the need to find new therapies for oral cancer,” Kapila said. “The use of small antibacterial agents, like nisin, to treat cancer is a new approach that holds great promise. Nisin is a perfect example of this potential because it has been used safely in humans for many years, and now the laboratory studies support its anti-tumor potential.”

The U-M study, which looked at the use of antimicrobials to fight cancerous tumors, suggests nisin, in part, slows cell proliferation or causes cell death through the activation of a protein called CHAC1 in cancer cells, a protein known to influence cell death.

The study is the first to show CHAC1’s new role in promoting cancer cell death under nisin treatment. The findings also suggest that nisin may work by creating pores in the cancer cell membranes that allow an influx of calcium. It’s unclear what role calcium plays in nisin-triggered cell death, but it’s well known that calcium is a key regulator in cell death and survival.

Additionally, the findings suggest that nisin slows or stops tumor growth by interrupting the cell cycle in “bad” cells but not the good cells; thus nisin stops cancer cell proliferation but doesn’t hurt good cells.

Study suggests too much risk associated with SSRI usage and pregnancy

Antidepressants should only be prescribed with great caution

BOSTON – Elevated risk of miscarriage, preterm birth, neonatal health complications and possible longer term neurobehavioral abnormalities, including autism, suggest that a class of antidepressants known as selective serotonin reuptake inhibitors (SSRI) should only be prescribed with great caution and with full counseling for women experiencing depression and attempting to get pregnant, say researchers at Beth Israel Deaconess Medical Center, Tufts Medical Center and MetroWest Medical Center.

“Depression and infertility are two complicated conditions that more often than not go hand in hand. And there are no definitive guidelines for treatment,” says lead author Alice Domar, Ph.D, Obstetrics and Gynecology, Beth Israel Deaconess Medical Center and Executive Director of the Domar Center for Mind/Body Health at Boston IVF. “We hope to provide a useful analysis of available data to better inform decisions made by women and the providers who care for them.”

Domar and colleagues conducted a review of published studies evaluating women with depressive symptoms who took antidepressants while pregnant. The results appear online October 31 in the journal Human Reproduction.

“There are three main points that stand out from our review of the scientific studies on this topic,” says senior author Adam Urato, MD, Chairman of Obstetrics and Gynecology at MetroWest Medical Center and a Maternal-Fetal Medicine specialist at Tufts Medical Center. “First, there is clear and concerning evidence of risk with the use of the SSRI antidepressants by pregnant women, evidence that these drugs lead to worsened pregnancy outcomes. Second, there is no evidence of benefit, no evidence that these drugs lead to better outcomes for moms and babies. And third, we feel strongly that patients, obstetrical providers, and the public need to be fully aware of this information.”

Over the last 20 years antidepressant usage has increased 400 percent. Antidepressants are now the most commonly prescribed medication in the United States for people between 18 and 44 years of age, the childbearing years for most women. And as women enter their late 30s and early 40s they are more likely to experience infertility.

“According to the Centers for Disease Control, more than 1 percent of the babies born in the USA each year are the result of an IVF cycle,” write the authors. “And most women will report symptoms of depression during infertility treatment, especially following unsuccessful treatment cycles.”

As many as 11 percent of women undergoing fertility treatment report taking an SSRI to combat depressive symptoms, but Domar and colleagues found no evidence of improved pregnancy outcomes with antidepressant usage, and in fact, found the opposite. They also found plenty of controversy around SSRI efficacy. Many studies found SSRIs to be no more effective or only slightly more effective than placebos in treating depression. “More broadly, there is little evidence of benefit from the antidepressants prescribed for the majority of women of childbearing age–and there is ample evidence of risk,” the authors write.

For starters, there is mounting evidence that SSRIs may decrease pregnancy rates for women undergoing fertility treatment. Additionally, studies consistently show that women using antidepressants experience increased rates of miscarriage. There is also a strong signal of congenital abnormalities, the most noted of which is the association between the use of the antidepressant, Paxil, and cardiac defects. In 2005, this association prompted the FDA to ask Paxil’s manufacturer, GlaxoSmithKline to change Paxil’s risk factor from a C to a D, where a D rating indicates a demonstrated risk to the fetus.

“Preterm birth is, perhaps, the most pressing obstetrical complication,” write the authors. In more than 30 studies, the evidence overwhelmingly points to increased risk for early delivery in women who are taking antidepressants. “This is a significant finding because we know that babies born before 37 weeks are at risk for many short and long-term health problems,” says Urato. “Caring for premature babies adds up to billions of dollars in healthcare expenditures.”

Available data also suggests that antidepressant usage, especially if it extends beyond the first trimester, leads to an increased risk of pregnancy-induced hypertension and preeclampsia. “Given the importance of the hypertensive disorders of pregnancy in terms of maternal and newborn morbidity and mortality, and the widespread use of antidepressants during pregnancy, further investigation into this area will be essential,” write the authors.

The health complications associated with antidepressant usage can be carried into infancy and beyond. A 2006 study showed that infants exposed to antidepressants in utero had a 30 percent risk of Newborn Behavioral Syndrome, most commonly associated with persistent crying, jitteriness and difficulty feeding. In more rare instances the syndrome can produce seizures and breathing difficulties leading to the need for intubation. Studies have also shown delayed motor development in babies and toddlers. And a Kaiser Permanente study showed a “two-fold increased risk of autism spectrum disorders associated with maternal treatment with SSRI antidepressants during the pregnancy, with the strongest effect associated with treatment during the first trimester.”

“There is enough evidence to strongly recommend that great caution be exercised before prescribing SSRI antidepressants to women who are pregnant or who are attempting to get pregnant, whether or not they are undergoing infertility treatment,” says Domar. “We want to stress that depressive symptoms should be taken seriously and should not go untreated prior to or during pregnancy, but there are other options out there that may be as effective, or more effective than SSRIs without all the attendant risks.”

Domar and team looked at studies assessing different treatment modalities for depression in the general population, including psychotherapy, exercise, relaxation training, yoga, acupuncture and nutritional supplements. While many of these options were shown to provide some benefit, psychotherapy, specifically cognitive behavioral therapy (CBT) showed the most promise. “There is overwhelming evidence that CBT is equivalent to antidepressant medication in the treatment of mild to moderate depression and more recent research indicates that it is effective in the treatment of severe depression as well,” write the authors.

A 2008 study showed impressive results for CBT in depressed women undergoing infertility treatments. The results showed that 79 percent of women who received CBT reported a significant decrease in symptoms, compared with 50 percent of women in the medication group.

“These alternative treatment options may not be appropriate for everyone, still we think it’s important for women on an antidepressant who are considering becoming pregnant to have a conversation with their physician about the risks and benefits of continuing to take their medication,” says Domar. “Because at this point in time, with no data to indicate an advantage to taking an SSRI during pregnancy, the research all points to increased risk.”

Men who do exercise produce better quality semen

A new study conducted by researchers at the University of Cordoba links moderate physical activity in males with better hormone levels and sperm characteristics that favour reproduction compared to sedentary men.

Semen quality at large has dropped in the last 50 years. Amongst other factors, this is due to exposure to external agents alcohol and tobacco consumption. This decline in sperm properties has caused an increase in reproductive problems.

Therefore, experts have studied the possible relationship between sperm quality and lifestyle habits in males. Published in the ‘European Journal of Applied Physiology‘, the new study suggests that men who do moderate physical exercise have better hormone levels and their gonads undergo healthier spermatological processes.

The authors assessed whether there was a difference in the hormonal and seminoligical profiles of physically active and sedentary males. “We have analysed qualitative semen parameters like the ejaculated volume, sperm count, mobility and sperm morphology,” as explained to SINC by Diana Vaamonde, researcher at the University of Cordoba and lead author of the study.

In addition, an evaluation was made of the follicle-stimulating hormone (FSH), the luteinising hormone (LH), testosterone (T), cortisol (C) and the T/C ratio. This offers additional information on the environment needed for the sperm creation process as well as the anabolic or catabolic state of the body.

“Despite the fact that the sample population is not very big (31 men), given the complexity of the analysis, this is the first study that assessed the differences between these parameters in both populations,” states the researcher.

The results conclude that the physically active subjects display better semen values. More specifically, the differences found were in the seminological parameters of total progressive velocity and morphology, in the FSH, LH and T hormones and in the T/C ratio. Hormone data thus supports the hypothesis of a more favourable environment for sperm formation.

Moderate exercise is the key

In 2010, the same researcher published a study showing that the sperm parameters of elite sportsmen (triathletes and waterpolo players) are worse than men who are just physically active. It is possible that the increased strain of training causes a decline in sperm quality.

“Despite that fact that more studies are needed to confirm these findings, we can suggest exercise to improve the hormonal environment and stimulate the sperm process,” adds Vaamonde.

Green tea found to reduce rate of some GI cancers

Women who drink green tea may lower their risk of developing some digestive system cancers, especially cancers of the stomach/esophagus and colorectum, according to a study led by researchers from Vanderbilt-Ingram Cancer Center.

The study by lead author Sarah Nechuta, Ph.D., MPH, assistant professor of Medicine, was published online in advance of the Nov. 1 edition of the American Journal of Clinical Nutrition. Wei Zheng, M.D., Ph.D., MPH, professor of Medicine, chief of the Division of Epidemiology and director of the Vanderbilt Epidemiology Center, was the principal investigator for the study.

To determine green tea’s impact on cancer risk, the investigators surveyed women enrolled in the Shanghai Women’s Health Study, a population-based study of approximately 75,000 middle-aged and older Chinese women. During the initial interview participants were asked if they drank tea, the type of tea consumed and how much they consumed. Most of the Chinese women reported drinking primarily green tea.

The researchers found that regular tea consumption, defined as tea consumption at least three times a week for more than six months, was associated with a 17 percent reduced risk of all digestive cancers combined. A further reduction in risk was found to be associated with an increased level of tea drinking. Specifically, those who consumed about two to three cups per day (at least 150 grams of tea per month) had a 21 percent reduced risk of digestive system cancers.

The trend toward fewer digestive cancers was strongest for stomach/esophageal and colorectal cancers.

“For all digestive system cancers combined, the risk was reduced by 27 percent among women who had been drinking tea regularly for at least 20 years,” said Nechuta. “For colorectal cancer, risk was reduced by 29 percent among the long-term tea drinkers. These results suggest long-term cumulative exposure may be particularly important.”

Tea contains polyphenols or natural chemicals that include catechins like EGCG and ECG. Catechins have antioxidant properties and may inhibit cancer by reducing DNA damage and blocking tumor cell growth and invasion.

The researchers also asked about other lifestyle factors including the kinds of food eaten regularly, exercise habits, education level and occupation. Women who had ever smoked or who drank alcohol were excluded from the study.

Regular tea drinkers in the study were younger, had higher education, exercised more and consumed more fruits and vegetables. While the researchers adjusted for these factors, they could not rule out an effect from these and other unmeasured lifestyle habits.

The study was conducted in nonsmoking and nondrinking Chinese women to minimize the potential influence of these two risk factors on the results for tea consumption and digestive system cancer risk.

Researchers discover watching horror films can help you burn equivalent of a chocolate bar, with The Shining burning most

Ben Child

guardian.co.uk, Monday 29 October 2012 09.53 EDT

Watching scary movies can help you burn the calorific equivalent of a small chocolate bar, according to a new study by researchers at the University of Westminster.

Those who watched a 90-minute horror film were likely to burn up to 113 calories – the same sort of figure as a half-hour walk. Some movies were more effective than others, however: of the 10 films studied, the top calorie-burners were the classic Stanley Kubrick chiller The Shining (184 calories), Jaws (161 calories) and The Exorcist (158 calories).

The study found that films with regular “jump-scare” moments were most likely to help burn calories because they increased the heart rate dramatically. “Each of the 10 films tested set pulses racing, sparking an increase in the heart rate of the case studies,” said Dr Richard Mackenzie, senior lecturer and specialist in cell metabolism and physiology at the university. “As the pulse quickens and blood pumps around the body faster, the body experiences a surge in adrenaline. It is this release of fast-acting adrenaline, produced during short bursts of intense stress (or in this case, brought on by fear), which is known to lower the appetite, increase the basal metabolic rate and ultimately burn a higher level of calories.”

Scientists measured heart rate, oxygen intake and carbon dioxide output for the study, which was commissioned by the movie rental firm Lovefilm. They discovered that the number of calories used increased, on average, by a third during the screenings.

“We all know the feeling of wanting to hide behind the sofa or grab a pillow when watching scary or hair-raising scenes,” said Lovefilm editor Helen Cowley. “But this research suggests that maybe those seeking to burn some calories should keep their eyes on the screen.”

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